2 research outputs found
Hemoglobin-derived Peptides as Novel Type of Bioactive Signaling Molecules
Most bioactive peptides are generated by proteolytic cleavage of large precursor proteins followed by storage in secretory vesicles from where they are released upon cell stimulation. Examples of such bioactive peptides include peptide neurotransmitters, classical neuropeptides, and peptide hormones. In the last decade, it has become apparent that the breakdown of cytosolic proteins can generate peptides that have biological activity. A case in point and the focus of this review are hemoglobin-derived peptides. In vertebrates, hemoglobin (Hb) consists of a tetramer of two Ξ±- and two Ξ²-globin chains each containing a prosthetic heme group, and is primarily involved in oxygen delivery to tissues and in redox reactions (Schechter Blood 112:3927β3938, 2008). The presence of Ξ±- and/or Ξ²-globin chain in tissues besides red blood cells including rodent and human brain and peripheral tissues (Liu et al. Proc Natl Acad Sci USA 96:6643β6647, 1999; Newton et al. J Biol Chem 281:5668β5676, 2006; Wride et al. Mol Vis 9:360β396, 2003; Setton-Avruj Exp Neurol 203:568β578, 2007; Ohyagi et al. Brain Res 635:323β327, 1994; Schelshorn et al. J Cereb Blood Flow Metab 29:585β595, 2009; Richter et al. J Comp Neurol 515:538β547, 2009) suggests that globins and/or derived peptidic fragments might play additional physiological functions in different tissues. In support of this hypothesis, a number of Hb-derived peptides have been identified and shown to have diverse functions (Ivanov et al. Biopoly 43:171β188, 1997; Karelin et al. Neurochem Res 24:1117β1124, 1999). Modern mass spectrometric analyses have helped in the identification of additional Hb peptides (Newton et al. J Biol Chem 281:5668β5676, 2006; Setton-Avruj Exp Neurol 203:568β578, 2007; Gomes et al. FASEB J 23:3020β3029, 2009); the molecular targets for these are only recently beginning to be revealed. Here, we review the status of the Hb peptide field and highlight recent reports on the identification of a molecular target for a novel set of Hb peptides, hemopressins, and the implication of these peptides to normal cell function and disease. The potential therapeutic applications for these Hb-derived hemopressin peptides will also be discussed